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Biomedical subjects

A H Khan

Publications and source records attributed to A H Khan.

At least 37 records · Page 2Linked to original sources

Fertility of the cysts of Echinococcus granulosus in domestic herbivores from Benghazi, Libya, and the reactivity of antigens produced from them.

Unilocular cysts produced by Echinococcus granulosus were recovered from 110 domestic herbivores (60 sheep, 25 cattle, 20 goats and five camels) slaughtered in Benghazi. The proportion of the cysts from the sheep found to be fertile (75%) was higher than that of the cysts from the goats (55%), camels (40%), or cattle (0%). When tested in indirect haemagglutination assays (IHA) with eight sera from human cases of cystic echinococcosis, the fluid from the cattle cysts never gave a positive reaction. Antigens in the fluids collected from sheep or goat cysts did react with the sera, with antigens from each of the two sources giving similar titres with each serum. However, crude somatic antigens (prepared from protoscolices and brood capsules collected from sheep cysts) appeared to be more sensitive for the immunodiagnosis of human cystic echinococcosis than the cyst-fluid antigens.

Animals↗

Morphological spectrum of ophthalmic tumors in northern Pakistan.

OBJECTIVE: The objective of the study was to assess the frequency and pattern of ophthalmic tumours in Northern Pakistan. METHODS: This study included all ophthalmic tumours diagnosed during a one year period (January to December 1992). RESULTS: One hundred and fourteen ophthalmic tumours were diagnosed at the Armed Forces Institute of Pathology (AFIP) and Pathology Department of the Army Medical College (AMC), Rawalpindi. Of these tumours, 70 were malignant (61.5%) and 44 were benign (38.5%). The age distribution of malignant ophthalmic tumours had two peaks. The first was seen in the paediatric age group and was mainly due to retinoblastoma. The second peak was seen above 50 years of age and was mainly due to conjunctival squamous cell carcinoma and malignant eyelid tumours which constituted 85% of the malignant ophthalmic tumours in paediatric age group. The average age at presentation of retinoblastoma was 3.8 years. The average age at presentation for squamous cell carcinoma was 56 years. Basal cell carcinoma was the most common malignant eyelid tumour (55%). The most common extraocular malignant orbital tumour was non-Hodgkin's lymphoma. Malignant melanoma of the uvea formed 22% of all melanomas diagnosed during this period. The most common benign tumours were naevi (33%), epidermal inclusion cysts (18%), choristomata (16%) and haemangioma (8%). The malignant ophthalmic tumours constituted 3% of all the malignant tumours diagnosed in Northern Pakistan during 1992 at AFIP and AMC, Rawalpindi. CONCLUSION: The ophthalmic tumours, both benign and malignant are not infrequent in clinical practice in Northern Pakistan.

Adolescent↗

Munc18c regulates insulin-stimulated glut4 translocation to the transverse tubules in skeletal muscle.

To examine the intracellular trafficking and translocation of GLUT4 in skeletal muscle, we have generated transgenic mouse lines that specifically express a GLUT4-EGFP (enhanced green fluorescent protein) fusion protein under the control of the human skeletal muscle actin promoter. These transgenic mice displayed EGFP fluorescence restricted to skeletal muscle and increased glucose tolerance characteristic of enhanced insulin sensitivity. The GLUT4-EGFP protein localized to the same intracellular compartment as the endogenous GLUT4 protein and underwent insulin- and exercise-stimulated translocation to both the sarcolemma and transverse-tubule membranes. Consistent with previous studies in adipocytes, overexpression of the syntaxin 4-binding Munc18c isoform, but not the related Munc18b isoform, in vivo specifically inhibited insulin-stimulated GLUT4-EGFP translocation. Surprisingly, however, Munc18c inhibited GLUT4 translocation to the transverse-tubule membrane without affecting translocation to the sarcolemma membrane. The ability of Munc18c to block GLUT4-EGFP translocation to the transverse-tubule membrane but not the sarcolemma membrane was consistent with substantially reduced levels of syntaxin 4 in the transverse-tubule membrane. Together, these data demonstrate that Munc18c specifically functions in the compartmentalized translocation of GLUT4 to the transverse-tubules in skeletal muscle. In addition, these results underscore the utility of this transgenic model to directly visualize GLUT4 translocation in skeletal muscle.

Animals↗

A genetic screen for novel behavioral mutations in mice.

A genetic screen using mice was performed to identify dominant loci affecting behavior. Mice were mutagenized with ENU, then bred to examine their G1 offspring for behavioral abnormalities. Potentially mutant G1 pups were screened through a variety of behavioral assays, including tests of learning and memory, sensorimotor gating, fear and anxiety, nociception (pain perception) and locomotor activity. Mice falling outside the normal performance distribution in these tests were considered potential behavioral mutants and were bred for further analysis. Outliers included both animals with very discrete defects and animals with abnormal performance across a range of tests. To date, we have identified two confirmed mutants affecting sensorimotor gating. These results provide further impetus for the use of random mutagenesis screens as a tool for dissecting the genetic basis of brain and behavior.

Alkylating Agents↗

Munc18c function is required for insulin-stimulated plasma membrane fusion of GLUT4 and insulin-responsive amino peptidase storage vesicles.

To examine the functional role of the interaction between Munc18c and syntaxin 4 in the regulation of GLUT4 translocation in 3T3L1 adipocytes, we assessed the effects of introducing three different peptide fragments (20 to 24 amino acids) of Munc18c from evolutionarily conserved regions of the Sec1 protein family predicted to be solvent exposed. One peptide, termed 18c/pep3, inhibited the binding of full-length Munc18c to syntaxin 4, whereas expression of the other two peptides had no effect. In parallel, microinjection of 18c/pep3 but not a control peptide inhibited the insulin-stimulated translocation of endogenous GLUT4 and insulin-responsive amino peptidase (IRAP) to the plasma membrane. In addition, expression of 18c/pep3 prevented the insulin-stimulated fusion of endogenous and enhanced green fluorescent protein epitope-tagged GLUT4- and IRAP-containing vesicles into the plasma membrane, as assessed by intact cell immunofluorescence. However, unlike the pattern of inhibition seen with full-length Munc18c expression, cells expressing 18c/pep3 displayed discrete clusters of GLUT4 abd IRAP storage vesicles at the cell surface which were not contiguous with the plasma membrane. Together, these data suggest that the interaction between Munc18c and syntaxin 4 is required for the integration of GLUT4 and IRAP storage vesicles into the plasma membrane but is not necessary for the insulin-stimulated trafficking to and association with the cell surface.

Adipocytes↗

Biochemical profiles of hydatid cyst fluids of Echinococcus granulosus of human and animal origin in Libya.

A comparative study on the biochemical parameters in hydatid cyst fluids of sheep, goats, camels, cattle and human cystic forms of Echinococcus granulosus has been made in Libya. Quantitative variations in the levels of sodium, potassium, calcium, cholesterol, glucose, urea, creatinine and gamma glutamyl transpeptidase (gamma GT) were found in the cystic fluids of different host origins although these differences were statistically insignificant compared with the hydatid fluids of sheep. However, the concentration of triglycerides and proteins were significantly elevated in the cyst fluids of sheep compared with the other fluids studied. Similarities in the biochemical composition of different hydatid cyst fluids suggest the existence of sheep strains of E. granulosus in human and other domestic animal intermediate hosts in Libya.

Animals↗

Prevalence of Helicobacter pylori antibodies in endoscopy personnel and non-medical volunteers of Karachi.

Prevalence of Helicobacter pylori (Hp) is high in developing countries. As endoscopy personnel are at greater risk of exposure to gastric secretions, they are apparently at higher risk of acquiring this infection. The aim of this study was to determine prevalence of Hp antibodies in endoscopy staff and compare it with non-medical volunteers and assess any additional risk of occupational exposure to Hp in the former group. Thirty-three subjects working in endoscopy suites of different hospitals of Karachi and 33 non-medical volunteers were investigated for the prevalence of Hp antibodies by using a commercially available rapid qualitative test (FlexPack HP; Abbott). The two groups were comparable in mean age, sex and social class. Twenty-six of 33 (79%) of the endoscopy personnel and 19/33 (58%) of the non-medical volunteers were positive for Hp serology (p = 0.06 R.R 1.37). Among the endoscopy personnel 13/14 (93%) of endoscopy assistants were positive and this subgroup had a significantly higher prevalence of Hp antibodies as compared to the control group (p = 0.019). No correlation could be found between the positive serology and symptoms of dyspepsia.

Adult↗

Role of serum angiotensin converting enzyme in sarcoidosis.

This study was conducted to determine the role of Serum Angiotensin Converting Enzyme (SACE) as a marker in the differential diagnosis of pulmonary diseases and prognosis of sarcoidosis. A retrospective analysis of 113 medical records of patients at The Aga Khan University Hospital, with laboratory investigation for SACE was performed. Among 113 patients, 51 cases were found to have sarcoidosis, 44 of them had SACE levels greater than 52 IU/L (mean ACE 104.44). SACE levels were also found elevated in other clinical conditions like tuberculosis (mean 58.64 IU/L), but the enzyme level were less (p 0.04) than those found in sarcoidosis (mean (92.97 IU/L). SACE activity was found to be considerably lower in other chronic lung diseases such as, fibrosing alveolitis (mean 43.98 IU/L), interstitial lung disease (mean 42.11 IU/L) and chronic obstructive lung disease (mean 40.85 IU/L). Twenty patients of sarcoidosis, who received steroid treatment subsequently showed a decline in the SACE levels. SACE is a useful marker in differential diagnosis as 37.2% cases of sarcoidosis compared to only 9.09% of tuberculosis had SACE levels greater than 100 IU/L. In addition, our data also suggest that serum ACE is useful for the diagnosis as well as monitoring prognosis in sarcoidosis.

Adult↗

Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: epidemiological correlations.

To investigate the potential relationship of socioeconomic status with the prevalence of Epstein-Barr virus (EBV) and to understand the significance of del-LMP-1 within EBV+ cases of Burkitt's lymphoma (BL), we studied 10 cases of BL, 30 cases of diffuse large cell lymphoma (DLCL) arising in nonimmunocompromised patients, and 30 reactive tonsillar biopsy specimens from Pakistan. Each lymphoma was analyzed for EBV by EBER1 RNA in situ hybridization (EBV-RISH). Cases showing hybridization signal within neoplastic cells and all reactive tonsillar tissues were analyzed for EBV strain type by EBNA-2 polymerase chain reaction (PCR) and for the presence of a del-LMP-1 by PCR. Eight of 10 (80%) of BL were EBV+, each containing EBV strain A and a wild-type LMP-1 gene. In contrast, only 4 of 30 DLCL (13%) cases were EBV positive (three strain A, one strain B), each containing a wild-type LMP-1 gene. Fifteen of 30 tonsillar biopsy specimens contained EBV, all of which were strain A and wild-type for LMP1. The prevalence of EBV in BL from Pakistan is slightly lower than in BL in endemic regions, but significantly higher than in BL in North America. EBV positivity probably reflects the socioeconomic status of the patient population and age at seroconversion. The absence of del-LMP-1 within all EBV+ BL cases is consistent with the view that del-LMP-1 is not involved in the pathogenesis of BL, and the presence of del-LMP-1 in EBV+ cases of BL reported in other studies may likely reflect the prevalence of a viral strain containing the 30-bp deletion within the respective population studied.

Adolescent↗

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in amoebic liver abscess.

We report here three cases of amoebic liver abscess with biochemical abnormalities of syndrome of inappropriate secretion of antidiuretic hormone (SIADH). All three patients were febrile and had pain in the right upper abdomen radiating to the right shoulder. Liver function tests were disturbed. Chest X-ray showed raised right hemidiaphragm with obliteration of the right costophrenic angle. On ultrasound, an abscess 710 cm in diameter was located in the upper right lobe. SIADH was transient and improved with treatment. We believe this to be the first reported association of SIADH with amoebic liver abscess.

Adult↗

Carbohydrate moiety of Plasmodium falciparum glycoproteins: the nature of the carbohydrate-peptide linkage in the MSP-2 glycoprotein.

Metabolic labelling of Plasmodium falciparum parasites with [3H]GlcN, [3H]Man, [3H]Gal and [3H]ethanolamine, and subsequent purification by SDS-PAGE of the labelled material provided effective labelling of the MSP-1, 195 kDa, and MSP-2, 42-53 kDa, glycoproteins. Reductive beta-elimination of the MSP-2 released from the gel consisted of glycopeptides containing labelled sugars. Processing of the eliminated components and identification of the sugar residues demonstrated the presence of N-acetylglucosaminitol and N-acetylgalactosaminitol amongst other labelled sugars. Reductive beta-elimination with sodium hydroxide-sodium borotritide-borohydride showed the presence of glucosaminitol and alanine in the hydrolysis products. The MSP-2 was retained on solid phase wheat-germ agglutinin and was released from the lectin by treatment with GlcNAc. Upon treatment with O-glycanase the MSP-2 glycoprotein released labelled amino sugar, and derived oligosaccharides on treatment with exoglycosidases released labelled components corresponding to the metabolically incorporated sugars. Labelled Gal was incorporated into the MSP-2 glycoprotein using [3H]UDP-Gal and galactosyltransferase. The galactosylated glycoprotein released labelled Gal upon treatment with beta-galactosidase. The results of the present study suggest that the carbohydrate chains of the MSP-2 glycoprotein are attached to the protein backbone via GlcNAc- and GalNAc-serine/threonine in O-glycosyl linkage and the glycoprotein has terminal GlcNAc and Gal residues. The carbohydrate moieties of MSP-2, glycoprotein consist mainly of short chains linked to the protein core.

Animals↗